Scheme 1.

Schematic illustration of the role of platelet in the whole tumor metastasis cascade. (A) Platelets-promoted tumor metastasis cascade. Platelets can be activated and attach to cancer cells to generate a protective cloak that helps cancer cells to escape immune surveillance and high shear stress from the bloodstream. Additionally, activated platelets could help circulating tumor cells (CTC) arrest by vessel endothelial cells, and CTC extravasation through blood vessels, and provide aid to metastatic lesion growth. (B) Nanoplateletsomes (P-Lipo) inhibit metastasis formation through active targeting and act as a decoy to inhibit the function of platelets. The designed P-Lipo could bind with CTCs, interfere with CTC arrest by vessel endothelial cells, CTC extravasation through endothelial layers, and epithelial-mesenchymal transition of tumor cells. More importantly, P-Lipo could decrease CTC survival in the blood and counteract metastatic tumor growth efficiently by inhibiting the inflammation and suppressing CTC escape.